Opioids Flashcards
1
Q
What is the simple definition for opioids?
A
any ligand for opiod receptors
2
Q
Give some general knowledge about Opioids?
A
- Opioid drugs are narcotic analgesics: they reduce pain but do not produce unconsciousness
- They are the most effective painkillers known
- They also create a feeling of relaxation, euphoria, and sleep
- At high doses they can induce coma and death
3
Q
What are the origins of Opium?
A
- Opium is an extract of the poppy plant (Papver somniferum)
- Most of these plants are grown in Southeast Asia, India, China, Iran, Turkey, and southeastern Europe
- They have a very long history of use, with both recreational and medical use dating back thousands of years
4
Q
What are some historic uses of opium?
A
- Descriptions date back to the early 3rd century B.C.
- Galen (130 - 200 AD) recommended it for medicinal purposes (loss of voice, asthma, deafness)
- Arabs also used it for various medicinal purposes (including diarrhea)
- Spread to India and China
- 11th and 12th centuries crusaders brough it back to Western Europe
5
Q
What is Laudanum?
A
- Laudanum is an opium-based medicinal drink which was introduced in England in 1680
- Drinking laudanum-laced wine was the accepted form of opium use in Victorian England and Ameica
- Especially women
- Up to the twentieth century, laudanum was common in popular remedies
6
Q
What is opium’s history in the United States?
A
- Opium was cultivated in Vermont, New Hampshire, Florida, Louisiana, California and Arizona
- It was grown legally until 1942
- Women drunk it more than men
- Smoking was not socially accepted
- In 1875 San Francisco outlawed opium smoking
- Largely due to anti-Chinese attitude
7
Q
How did morphine originate?
A
- Morphine was isolated in 1803
- 10X more potent than raw opium
- 1856, the hypodermic syringe was invented
- During the American Civil War (1861-1865) many soldiers became dependent (“the soldier’s disease”)
8
Q
How did Heroin originate?
A
- Bayer introduced heroin in market in 1898
- Heroin is 3X stronger than morphine
- In 1910 they realized that it was addictive
9
Q
How is morphine made?
A
- Morphine is one of the typical opiates and is a natural product
- Extracted from poppy plant by cutting surface of seed pod and harvesting the “milk” that comes out
- Morphine is part of this “milk” and can be purified from ti
10
Q
How is Heroin made?
A
- Heroin was made by adding two acetyl groups to morphine, making it more lipid soluble
- This reaches the brain faster, so it is much more potent than morphine, when injected
11
Q
What are semi-synthetic drivatives? entirely synthetic?
A
- Some opium derivatives are “semi-synthetic” chemically modiced versions of opium igredients
- Other narcotics are entirely sysnthetic and may have very different chemical structures.
12
Q
What are partial agonists?
A
**Partial agonists **are the product of modification to opium, they bind to receptrs but have less biological effect.
13
Q
What are pure antagonists?
A
**Pure antagonists, **such as naloxone and nalorphine, are structurlaly similar but have no efficary. They can prevent or reverse the effect of opioids.
14
Q
What are some Opiate Effects?
A
- Pain reduction
- Produce euphoria
- Also cause tolerance and addiction
- Promote relaxation
- Slow breathing
- At high dose can result in death
- Actws on bainstem’s respiratory center
- Cause constipation
- A reason for its use in treating diarrhea
- Constrict pupils
- Induce nausea and vomiting
- Thus, classic signs in emergency room is contricted pupils and depressed breathing
15
Q
Why does morphine cause vomiting?
A
Morphine affects the area postrema and thus elicits vomitings.
Recal we discussed the area postrema/chemical trigger zone when discussing the blood brani barrier.
16
Q
How does morphine relate Diarrhea?
A
- Morphine also affectsz the GI tract
- Opium and morphine have been used to treat diarrhea and can be life-saving to stop fluid loss in severe bacterial and parasitic diseases
- Unfortunately, when opioids are used for pain management, constipation is a common side effect.
17
Q
How do opiates relate to withdrawal?
A
- After developing physical addiction and tolerance, removal of the drug will result in:
- Dysphoria
- Craving for drug
- Diarrhea and vomiting
- Pain
- Sweating and tremors
- Mental confusion and memory deficits
18
Q
How can we treat opiate dependence?
A
- When addicted, two different drugs can be sued to reduce withdrawal
- Methadone is an opiate as well and can be administered to reduce drug craving
- In effect, it satisfies some of the drug cravins and thus reduces withdrawal effects
- Naltrexone is an opiate blocker/antagonist
- Will compete wit opioids for receptors and if given enough, opioids will have no effect
19
Q
What are some interesting facts?
A
- The potency of heroin and morphine is equivalent when take orally
- Heroin molecule is a slight modification of morphine (Diacetylmorphine)
- Heroin in the brain is metabolized into morphine
- Endogenous opioids (endorphin, enkephalin) are more potent than heroin
20
Q
How does opioid binding work?
A
- Bind to specific receptors for naturally occurrring opioid-like neurotransmitters
- Thus, basis of action is on a system that is already found in the brain
21
Q
Identifying the Recpetors (opioid)
A
- Opioid receptors were identified by radioligand binding methods.
- As the amount of radioactive opioid (e.g., the antagonist naloxone) is increased, binding increases and then tapers off until the receptors are fully occupied.
- Thus, there was no binding to other receptors, and binding was shown to be reversible.
22
Q
What are the receptor subtypes?
A
- Selective radioligands were used to identify receptor subtypes: mu, delta, kappa, and the nociceptin/orphanin FW receptor (NOP-R)
- The receptor subtypes have distinct distributions in the brain and spinal cord, suggesting that they mediate a wide variety of effects
23
Q
What do opioids bind to?
A
Opioids bind to opioid receptors in the brain -> endorphins
24
Q
What are 3 types of receptors?
A
- 3 types of receptors -> metabotropic
- mu
- delta
- kappa
25
Q
Opiates bind to receptors?
A
- Opiates bind to the receptors
- Analgesia-> medial thalamus, median raphe
- Reward (pleasure) -> limbic system
26
Q
How do receptors mediate the rewarding effects?
A
- Increase in dopamine release -> limbic system
- Euphoria
- Relaxed state
- Opiates can act
27
Q
How can opiates act to mediate the rewarding effects?
A
- Spinal cord
- inhibit the release of substance P between afferent neurons
- Brain: brain stem, thalamus, limbic system
- Involved in interpretation of pain and pain responses
- Opiates in the brain don’t block the pain messages
- They change the subjective experience of pain
28
Q
Describe the mu receptors?
A
- The mu receptor has a high affinity for morphine
- They are widely distributed in both the brain and spinal cord
- Location of mu-receptors reflect the effects of morphine
29
Q
What are some locations of the mu-receptors?
A
- Analgesia- [medial thalamus, periaqueductal gray, median raphe, spinal cord].
- Feeding and positive reinforcement- [nucleus accumbens].
- Cardiovascular and respiratory depression, cough control, nausea and vomiting- brainstem
- Sensorimotor integration- [thalamus, striatum].
30
Q
Describe delta-receptors:
A
- Delta-receptors are predominantly found in forebrain structures (fewer than mu).
- Many of these sites are consistent with a possible role for delta-receptors in modulating olfaction, motor integration, reinforcement, and cognitive function.
- Areas of overlap with mu-receptors suggest modulation of both spinal and supraspinal analgesia
31
Q
Describe Kappa-receptors:
A
- Kappa-receptors have distinct distribution
- Initially identified by binding to ketocyclazocine, and opioid analog that produces hallucinations and dysphoria
- Found in the striatum and amygdala, specific for hypothalamus and pituitary; may participate in regulation of pain perception, gut motility, and dysphoria (remember how hormones differ from neurotransmitters)
32
Q
What do we know about natural binding concerning opioids?
A
- The presence of receptors for opium derivaties suggested there might be endogenous opioid neurochemicals
- In the 1970s, endorphins- peptides that could bind to receptors- were identified
- Four large propeptides (precursor peptides) are processed into smaller active opioids
- Widespread location of the peptides implicate them in many functions, including pain suppression, reward, motor coordination, endcrine function, fedding, body temperatur and water regulation and response to stress
- The peptides are not selective for a receptor type but show only a relative preference.
